Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.

UBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF's effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.

Space-time mapping on the sagittal axis in congenital blindness.

Previous evolutionary perspectives proposed that the space-time mapping on the sagittal axis originates from visuo-locomotion coupling when walking/running forward. Accordingly, the congenitally blind could not have developed a sagittal mental timeline if the latter depends on such a visuo-locomotion coupling. However, this conclusion was reached in only a single empirical study (Rinaldi et al. in J Exp Psychol General 147:444-450, 2018), and its theoretical underpinnings are not entirely convincing as locally static and continuous auditory input undergoes a relatively similar change as function of self-locomotion, but this type of sensory-locomotion coupling is spared even in congenital blindness. Therefore, the present study systematically explored whether the congenitally blind show space-time mappings on the sagittal axis using different paradigms in three experiments. In Experiment 1, using a typical implicit RT task, the congenitally blind showed the same preferred space-time mapping in the sagittal dimension as normally sighted participants did. In Experiment 2, this space-time mapping occurred even automatically when temporal relations were task-irrelevant in a naming task. In Experiment 3, in an explicit space-time mapping task, the congenitally blind were more likely to locate the past behind and the future in front of their bodies. Moreover, most blind participants used spatial metaphors for their space-time mapping on the sagittal axis. These results supported the conclusion that the congenitally blind have a sagittal mental timeline, and that their sensory-locomotion coupling experience was either more similar to that of sighted participants or not critical for the space-time mapping. The present study, thus, also helps to clarify the origin of the sagittal mental timeline.

Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells.

BACKGROUND: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate. OBJECTIVES: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients. METHODS: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells. RESULTS: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients' 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability. CONCLUSION: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.

Diagnostic implications of lncRNA NORAD in breast cancer.

This study aimed to assess the expression levels of non-coding RNA activated by DNA damage (NORAD) in the cells, tissues, and serum of breast cancer (BRCA) patients and benign breast nodules and investigate its association with clinicopathological characteristics and prognosis in BRCA. NORAD was analyzed using TCGA-BRCA, GSE77308, Cellminer, and Sangerbox databases, revealing its significance in BRCA prognosis, immune microenvironment, and cell function. Serum samples from 38 BRCA patients, 80 patients with benign breast nodules (50 fibroadenoma and 30 breast adenosis cases), and 42 healthy individuals were collected from Zhejiang Xiaoshan Hospital. NORAD expression was quantified using quantitative reverse transcription PCR (RT-qPCR). Differential NORAD expression between benign and malignant breast nodules and its relationship to clinicopathological characteristics were assessed. NORAD demonstrated elevated expression in BRCA patient serum compared to healthy individuals and those with benign breast nodules (P < 0.05). Moreover, its expression correlated with TNM-stage, lymph node metastasis, and luminal classification. These findings highlight the elevated NORAD expression in BRCA patient serum and its correlation with clinicopathological characteristics, providing insights into its potential as a diagnostic biomarker or therapeutic target.

Does walking/running experience shape the sagittal mental time line?

A growing body of evidence suggested that time could be separately represented either on the lateral or sagittal axis. And the lateral mental time line has an origin associated with sensorimotor experience, e.g., reading/writing. However, it is still not clear whether the sagittal mental time line also originates from sensorimotor experience, e.g., walking/running. To address this question, we examined how the movement experience affected the space-time mapping on the lateral and sagittal axes using the virtual reality technique in two experiments. The results showed that the virtual movement experience had significant effects on the space-time mapping on the lateral axis (Experiment 1), but not on the sagittal axis (Experiment 2). This finding supported that the space-time mapping on the lateral axis does originate from sensorimotor experience, while the space-time mapping on the sagittal axis more likely originates from spatial metaphors in languages or other cultural experiences.

The Emerging Roles of circRNAs in Papillary Thyroid Carcinoma: Molecular Mechanisms and Biomarker Potential.

Papillary thyroid carcinoma (PTC) is a common endocrine malignant tumor. The incidence of PTC has increased in the past decades and presents a younger trend. Accumulating evidence indicates that circular RNAs (circRNAs), featured with non-linear, closed-loop structures, play pivotal roles in tumorigenesis and regulate cell biological processes, such as proliferation, migration, and invasion, by acting as microRNA (miRNA) sponges. Additionally, due to their unique stability, circRNAs hold promising potential as diagnostic biomarkers and effective therapeutic targets for PTC treatment. In this review, we systematically arrange the expression level of circRNAs, related clinical characteristics, circRNA-miRNA-mRNA regulatory network, and molecular mechanisms. Furthermore, related signaling pathways and their potential ability of diagnostic biomarkers and therapeutic targets are discussed, which might provide a new strategy for PTC diagnosis, monitoring, and prognosis.

Machine learning modeling and prognostic value analysis of invasion-related genes in cutaneous melanoma.

In this study, we aimed to develop an invasion-related risk signature and prognostic model for personalized treatment and prognosis prediction in skin cutaneous melanoma (SKCM), as invasion plays a crucial role in this disease. We identified 124 differentially expressed invasion-associated genes (DE-IAGs) and selected 20 prognostic genes (TTYH3, NME1, ORC1, PLK1, MYO10, SPINT1, NUPR1, SERPINE2, HLA-DQB2, METTL7B, TIMP1, NOX4, DBI, ARL15, APOBEC3G, ARRB2, DRAM1, RNF213, C14orf28, and CPEB3) using Cox and LASSO regression to establish a risk score. Gene expression was validated through single-cell sequencing, protein expression, and transcriptome analysis. Negative correlations were discovered between risk score, immune score, and stromal score using ESTIMATE and CIBERSORT algorithms. High- and low-risk groups exhibited significant differences in immune cell infiltration and checkpoint molecule expression. The 20 prognostic genes effectively differentiated between SKCM and normal samples (AUCs >0.7). We identified 234 drugs targeting 6 genes from the DGIdb database. Our study provides potential biomarkers and a risk signature for personalized treatment and prognosis prediction in SKCM patients. We developed a nomogram and machine-learning prognostic model to predict 1-, 3-, and 5-year overall survival (OS) using risk signature and clinical factors. The best model, Extra Trees Classifier (AUC = 0.88), was derived from pycaret's comparison of 15 classifiers. The pipeline and app are accessible at https://github.com/EnyuY/IAGs-in-SKCM.

Role of Guanxi (interpersonal relationship) in bribe-taking behaviors: evidence from China.

Bribery, an illegal conspiracy between two transactional parties, has a wide range of destructive effects on society. From an interpersonal interaction perspective, we explored how Guanxi (interpersonal relationships, including direct and indirect ones) influences individuals, especially government officials' bribe-taking probability, using behavioral experiments and questionnaires. The findings suggested that direct Guanxi promoted individuals' acceptance of bribes (Study 1a), and indirect Guanxi had the same role and effect sizes (Study 1b). However, the mechanisms were slightly different. Government officials were more likely to accept bribes from family members and friends (direct Guanxi) (than strangers) because they had more trust and felt more responsible and obligated to help them (Study 2). However, accepting bribes from those who contacted them through their family or friends (indirect Guanxi) (vs. strangers) was only driven by trust (Study 3). The present study explores the lubricant role of Guanxi in corruption, extends the literature on why bribery occurs from a new perspective, and provides suggestions for fighting corruption.

Regulation of LncRNAs and microRNAs in neuronal development and disease.

Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases.

Neural correlates of bribe-taking decision dilemma: An fNIRS study.

Bribe-taking decision is a social dilemma for individuals: the pursuit of economic self-interest vs. compliance with social norms. Despite the well-known existence of the conflict in deciding whether to accept bribes, little is known about its neural responses. Using functional near-infrared imaging (fNIRS) technology and the bribe-taking decision game (economic gambling game as a control condition), the current study dissociated the neural correlates of the different motivations in the bribery dilemma, as well as the inhibitory effect of social norms on bribery and its underlying brain mechanisms in supra-cortical regions. Findings revealed that if individuals are more motivated by economic interest, rejecting money (vs. accepting money) accompanies higher activity in the dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex (FPC), which reflects impulse inhibition and decision evaluation; whereas, if individuals are more consider social norms, their DLPFC is more active when they accept bribes (vs. reject bribes), which reflects their fear of punishment. Additionally, the key brain region where social norms inhibit bribery involves the left DLPFC. The current findings contribute to the literature on the neural manifestations of corrupt decisions and provide some insights into the anti-corruption movement.

Consumers' knowledge, attitude, and behavior towards antimicrobial resistance and antimicrobial use in food production in China.

Background: Antimicrobial resistance (AMR) can be induced by overuse or misuse of antimicrobials. Few researches were involved in consumers' knowledge and attitude toward antimicrobial use (AMU) in food production. This study was designed to investigate the knowledge and awareness, perception, and attitude of Chinese consumers toward AMU in food production. Their behavior, purchase intention of antimicrobial-free food products, and confidence in information sources were also investigated. Methods: As a descriptive cross-sectional study, an online electronic survey questionnaire was conducted between February 25 and March 8, 2022, involving 1,065 consumers in China. Factor analysis was conducted to identify underlying patterns of the attitudes and information sources. Spearman correlations were employed to determine the relationship between knowledge, attitudes and the intention to pay extra. The differences in knowledge and attitudes were performed by independent t-test and one-way analysis of variance (ANOVA) test, and the difference in intention was performed by Chi-square test, when compared with demographic factors. Results: The findings showed that even though 75.0% of them heard of AMR, and 48.2% knew the definition of AMR, the level of consumers' knowledge of AMU in farming production and food regulations in China was not high (48.9% of participants replied correctly). About half viewed AMU and AMR as a potential risk to their health. Of these participants, 61.3% claimed that they were more likely looking for specific information about AMU on food packaging, and 58.3% changed their eating or cooking habits due to the concern. In addition, 79.8% were willing to pay extra for antimicrobial-free food products. Information sources from professionals and authorities were considered more accurate than those from media, the internet, word of mouth, and others. Conclusions: Chinese consumers had insufficient knowledge and neutral attitudes about AMU in farming production and food regulations in China. A large proportion of the participants were willing to purchase antimicrobial-free food products. Most of them obtained related information from the media. This study highlighted the importance of updated education and effective communication with consumers in China. It helps to develop the reliable foodborne AMR surveillance system along food chain and improve government communication and consumer awareness.

System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases.

Renal cell carcinoma (RCC) is a type of cancer that develops in the renal epithelium of the kidney. It is responsible for approximately 3% of adult malignancies, and 90-95% of neoplasms originate from the kidney. Advances in tumor diagnosis, innovative immune therapeutics, and checkpoint inhibitors-based treatment options improved the survival rate of patients with RCC accompanied by different risk factors. RCC patients with diabetes, hepatitis C virus (HCV), or obesity (OB) may have a comorbidity, and finding the risk factor for better clinical treatment is an urgent issue. Therefore, the study focused on network-based gene expression analysis approaches to learning the impact of RCC on other comorbidities associated with the disease. The study found critical genetic factors and signal transduction pathways that share pathophysiology and commonly use dysregulated genes of the illness. Initially, the study identified 385 up-regulated genes and 338 down-regulated genes involved with RCC. OB, chronic kidney disease (CKD), type 2 diabetes (T2D), and HCV significantly shared 28, 14, 5, and 3 genes, respectively. RCC shared one down-regulated gene versican (VCAN) with OB and HCV and one down-regulated gene oxidase homolog 2 (LOXL2) with OB and CKD. Interestingly, most of the shared pathways were linked with metabolism. The study also identified six prospective biomarkers, signaling pathways, and numerous critical regulatory and associated drug candidates for the disease. We believe that the discovery will help explain these diseases' complicated interplay and aid in developing novel therapeutic targets and drug candidates.

Long Non-coding RNA UCA1 Regulates SRPK1 Expression Through miR- 99b-3p in Ovarian Cancer.

BACKGROUND: Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis. OBJECTIVE: In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC. METHODS: Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting. RESULTS: UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p. CONCLUSION: These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.

The synergistic antitumor effect of IL-6 neutralization with NVP-BEZ235 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) still ranks among the top cancers worldwide with high incidence and mortality. Due to abnormal activation of the PI3K/AKT/mTOR signalling pathway in HCC, targeting this pathway represents a potential therapeutic strategy. NVP-BEZ235 is a novel dual-targeted ATP-competitive PI3K/mTOR inhibitor that has shown effective antitumor effects. In this study, we found that interleukin-6 (IL-6) was significantly increased after exposure to NVP-BEZ235, and we proposed a treatment in which an anti-IL-6 antibody was combined with NVP-BEZ235 for HCC. In vitro results revealed that targeted inhibition of IL-6 potentiated the antitumor effects of NVP-BEZ235 in HCC cells. The mechanism might be attributed to their synergistic inhibitory activity on the PI3K/AKT/mTOR signalling pathway. Furthermore, an in vivo study demonstrated that combined administration of NVP-BEZ235 and anti-IL-6 Ab reduced HCC tumour load more effectively than either NVP-BEZ235 or anti-IL-6 Ab treatment alone. These findings add guidance value to the analysis of HCC and provide a reference for clinical treatment.

Long Non-coding RNA ZFPM2-AS1: A Novel Biomarker in the Pathogenesis of Human Cancers.

Due to their biological activities in regulating dosage compensation, epigenetics, and cell differentiation, long non-coding RNAs (lncRNA) have been recognized as important regulators of the beginning and development of human malignancies. LncRNA dysregulation has a significant impact on a range of cellular functions, including proliferation, migration, invasion, and anti-apoptosis activity. Recently, aberrant expression of the long non-coding RNA zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was observed in a range of solid tumors and correlated significantly with tumor size, histological differentiation, lymph node metastasis, malignant tumor (TNM) stage, short survival, and prognosis. Additional mechanical analysis indicated that ZFPM2-AS1 was involved in several cellular activities, including proliferation, migration, invasion, cell cycle progression, and apoptosis, through microRNAs (miRNAs), signaling pathways, and other biological components or proteins. This review summarizes the current status of research on ZFPM2-AS1 in various human malignancies and discusses its mechanism of action and clinical significance in tumor development and progression.

Advances in Pathophysiology of Triple-Negative Breast Cancer: The Potential of lncRNAs for Clinical Diagnosis, Treatment, and Prognostic Monitoring.

Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in several gene expression regulation processes, including epigenetic regulation, transcriptional regulation, post-transcriptional regulation, and translation regulation. It also plays a crucial role in the regulation of several characteristics of cancer biology, and the dysregulation of lncRNA expression in cancer may be part of the cause of cancer progression. Meanwhile, more and more studies are trying to determine the association between lncRNA expression and TNBC, as well as the functional role and molecular mechanism of the abnormally expressed lncRNA. Therefore, this review lists some abnormal lncRNAs in TNBC, further analyzes their molecular mechanisms and biological roles in the development of TNBC, and summarizes the potential of lncRNAs as biomarkers and therapeutic targets of TNBC, so as to provide ideas for clinical diagnosis, targeted therapy, and prognosis monitoring of TNBC.

A modified filter nonmonotone adaptive retrospective trust region method.

In this paper, aiming at the unconstrained optimization problem, a new nonmonotone adaptive retrospective trust region line search method is presented, which takes advantages of multidimensional filter technique to increase the acceptance probability of the trial step. The new nonmonotone trust region ratio is presented, which based on the convex combination of nonmonotone trust region ratio and retrospective ratio. The global convergence and the superlinear convergence of the algorithm are shown in the right circumstances. Comparative numerical experiments show the better effective and robustness.

miR-584 and miR-146 are candidate biomarkers for acute respiratory distress syndrome.

MicroRNAs (miRNAs/miRs) have important roles in inflammation and infections, which are common manifestations of acute respiratory distress syndrome (ARDS). The present study aimed to assess whether serum miRNAs are potential diagnostic biomarkers for human ARDS. For this, two sets of serum samples from healthy individuals and patients with ARDS were analysed by high-throughput sequencing to identify differentially expressed genes in ARDS. A total of 679 valid sequences were identified as differentially expressed (P<0.05). Of these, five differentially expressed miRNAs were subjected to reverse transcription-quantitative PCR validation. Finally, two miRNAs (miR-584 and miR-146a) were successfully verified. These two miRNAs were significantly downregulated in the serum of patients with ARDS. Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that their target transcripts were implicated in a broad range of biological processes and various metabolic pathways, including involvement in the regulation of various inflammatory factors. The present study provided a framework for understanding the molecular mechanisms of ARDS and suggested that miR-584 and miR-146a are associated with ARDS and may be potential therapeutic targets.

The internal representation of temporal orienting: A temporal pulse-accumulation and attentional-gating-based account.

Timing can be processed explicitly or implicitly. Temporal orienting is a typical implicit timing through which we can anticipate and prepare an optimized response to forthcoming events. It is, however, not yet clear whether mechanisms such as temporal-pulse accumulation and attentional gating (more attention, more accumulated temporal pulses) underly the internal representations of temporal orienting, as in explicit timing. To clarify this, a dual-task paradigm, consisting of a temporal orienting and an interference task, was adopted. Consistent with the temporal-pulse-accumulation and attentional-gating model, reaction times to the target detection of temporal orienting increased as the interference stimuli were temporally closer to the target, i.e., a location effect for temporal orienting. This effect is likely due to attention being diverted away from temporal orienting to monitor the occurrence of the interference stimuli for a longer time, resulting in greater temporal pulse loss and less accurate temporal orienting for conditions with later interference stimuli. The temporal-pulse-accumulation aspect in temporal orienting received further support by taking an explicit duration reproduction (containing a second temporal-pulse accumulation) as the interference task. On the one hand, temporal orienting became less accurate with increased temporal-pulse-accumulation overlaps between the dual tasks; on the other hand, two-way (one for temporal orienting and the other for duration reproduction), rather than one-way, location effects were observed, implying processing conflicts between the two temporal-pulse accumulations. Taken together, these results suggest that implicit and explicit timing may share common mechanisms upon internal temporal representations.

Small numerosity advantage for sequential enumeration on RSVP stimuli: an object individuation-based account.

Although there is a large literature demonstrating rapid and accurate enumeration of small sets of simultaneously presented items (i.e., subitizing), it is unclear whether this small numerosity advantage (SNA) can also manifest in sequential enumeration. The present study thus has two aims: to establish a robust processing advantage for small numerosities during sequential enumeration using a rapid serial visual presentation (RSVP) paradigm, and to examine the underlying mechanism for a SNA in sequential enumeration. The results indicate that a small set of items presented in fast sequences can be enumerated accurately with a high precision and a SOA (stimulus onset asynchrony)-sensitive capacity limit, essentially generalizing the large literature on small numerosity advantage from spatial domain to temporal domain. A resource competition hypothesis was proposed and confirmed in further experiments. Specifically, sequential enumeration and other cognitive process, such as visual working memory (VWM), compete for a shared resource of object individuation by which items are segregated as individual entities. These results implied that the limited resource of object individuation can be allocated within time windows of flexible temporal scales during simultaneous and sequential enumerations. Taken together, the present study calls for attention to the dynamic aspect of the enumeration process and highlights the pivotal role of object individuation in underlying a wide range of mental operations, such as enumeration and VWM.